What allows us to link particular visual stimuli with particular actions? We frequently and rapidly form different types of associations. Some associations can be as simple as learning that red means stop, while green means go. More complex associations can include a baseball player learning to swing at a pitch thrown in the strike zone. In general, humans and primates share a remarkable ability to rapidly adjust or modify associations between visual cues and specific motor responses in order to maximize reward. However, surprisingly little is known regarding how such associations are formed in the brain. Recent learning models suggest that the neostriatum, which is part of a larger group of nuclei called the basal ganglia, is optimally positioned to play a role in this process. Historically, studies of the basal ganglia have focused on their role in motor control. However, recent data suggests that the basal ganglia play a crucial role in associative learning. This new emphasis on learning takes into account data from both anatomic and physiologic studies and has the potential to unify what were previously disparate or paradoxical aspects of basal ganglia function. Therefore, the goal of the experiments described here is to systematically examine the role of the basal ganglia in learning new visual-motor associations using awake-behaving primates as our model. We will use a multidisciplinary approach involving novel behavioral learning tasks, direct microstimulation, and direct assessments of dopamine release, in order to elucidate the role of the neostriatum in associative learning. Our general hypothesis is that the dorsal neostriatum is a site where specific visual-motor associations are formed and enhanced. We believe that this process occurs by the reinforcement of particular circuits and that this reinforcement is mediated by the neurotransmitter dopamine. The results of this research will have profound implications for our comprehension of the brain mechanisms underlying learning and for our understanding of the role of the basal ganglia in general. Disruption of basal ganglia processing has been implicated in a number of disabling neurological diseases such as Parkinson Disease, Tourette syndrome and Autism. This proposal will shed considerable light on the role of basal ganglia in movement disorders and learning disorders. In addition, it will potentially provide the basis for their rational treatment using techniques such as deep brain stimulation. [unreadable] [unreadable] [unreadable]